Macrocyclic lactams of general formula VII wherein R1 is an amino protecting group and X is halogen. and particularly of formula VIII have been found to be potent inhibitors of HCV protease. Compound VIII is currently in preclinical development.

The key step in one synthesis of the macrocyclic compounds of formula VII is a ring closing metathesis (RCM) reaction of a diene compound in the presence of a suitable ring closing metathesis catalyst. PCT Publication WO 2005/037214 or PCT Publication
WO 2007/015824 discloses a diene of formula 2a can be subjected to RCM in the presence of a Nolan or Hoveyda catalyst to form the macrocyclic ester of formula 2b. Carbamoylation of the hydroxy substitutent is then carried out after the ring closure. Unfortunately the RCM as disclosed in the art suffers from modest yields and low catalyst selectivity, which translate into low efficiency and high costs.
There is a need for an improved process which is applicable on technical scale and which overcomes the limitations of the processes disclosed in the prior art.